Project Summary This is a high impact proposal with the overall goal to improve outcomes in aplastic anemia (AA). The disease consumes extensive resources and confers significant morbidity and mortality, due to their progressive nature and complications of suboptimal therapy. Without definitive treatment, mortality from severe AA approaches 70% at two years. Unfortunately, patients with acquired AA may have a response to immunosuppressive therapy (IST), but clonal evolution to myelodysplastic syndromes (MDS) or PNH develops in up to 40% of the patients, usually many months to years after the diagnosis of AA. This persistent clonal hematopoiesis is a challenge and requires further study in the patient population. The focus of this application is to identify the presence of somatic mutations in AA at varied times points in the disease. The literature suggests that clonal hematopoiesis is prevalent at diagnosis in AA but its correlation with disease phenotype and outcome is limited. This proposal, stemming from work done on Dr. DeZern?s K23, will greatly inform that knowledge in a select group of AA with known clinical responses.